The amyloid-β25-35 injection into the CA1 region of the neonatal rat hippocampus impairs the long-term memory because of an increase of nitric oxide

Alzheimer's disease (AD) is characterized by the amyloid-beta (Aβ) aggregation but it is unclear when this process begins. Previously, we showed that amyloid-β25-35 (Aβ(25-35)) increases the nitric oxide (NO) pathways and causes neurodegenerative effects in rats. The excessive increase of NO during brain development can promote a persistent oxidative stress, but the role of the Aβ(25-35) in the neonatal age and its effects over the long term is unclear. Our aim was to evaluate if the Aβ(25-35) injection on postnatal day 7 causes loss in spatial memory by NO pathways in adult rats. Our results showed that neonatal-Aβ(25-35) injection into the hippocampus (Hp) causes significant impairments in the spatial memory after 90 days. The NO levels were found increased and argynophilic in the Hp. Other evidence of neuronal damage was an increase of the immunoreactivity for 3-nitrotyrosine (3-NT) and the glial-fibrilar acid protein (GFAP) in the Hp of the Aβ(25-35) group. In contrast, these effects were blocked by the administration of L-NAME (inhibitor of nitric oxide synthase) before the injection of Aβ(25-35). The L-NAME plus Aβ(25-35) group showed a better performance in the spatial memory compared to the Aβ(25-35) group. In addition in this group we found a decrease of NO, 3-NT and neurodegeneration in the Hp compared to the Aβ(25-35) group. This finding is a novel result about the role of Aβ(25-35) during the neonatal stage that enhances the NO production, which appears to impair the spatial memory in adult rats.